Cholecystokinin (CCK) peptides are present in brain in high concentrations, and CCK and its specific receptors have been shown to be localized in such areas as cortex and hypothalamus. Recent evidence strongly suggests a role for brain CCK in the control of feeding behavior: CCK injected into the cerebral ventricles of sheep is a highly potent and specific suppressor of feeding. Of real physiological significance is the finding that satiety can be blocked by injection of CCK antiserum into the CSF. We have hypothesized that CCK is released in the brain during feeding, possibly secreted into the ventricular system and transported via CSF, and acts on CNS receptors involved in the elicitation of satiety. The proposed experiments will determine rates of release of CCK into CSF during hunger and satiety and determine sites of release as well as sites of action of brain CCK in causing satiety. In part one, the role of the ventricular system in the release, transport, and action of CCK will be studied. By first measuring changes in CSF concentration of endogenous CCK that occur during feeding and non-feeding periods, and then causing controlled changes by perfusing the ventricular system with solutions of increasing CCK concentrations, the importance of the ventricular system in CCK-elicited satiety will be determined. Perfusions of specific ventricular compartments will be carried out to determine those in closest proximity to CCK satiety receptors. In the second part, the role of specific brain sites in the release and action of CCK will be studied. Concentration of CCK in localized areas will be measured to determine whether changes occur during feeding and fasting. Microinjections of CCK and a specific CCK receptor antagonist, and push-pull perfusions of specific brain sites will be carried out to determine sites of action as well as sites of release of CCK in the brain. Thus, these experiments will provide additional information necessary to establish the physiological role of CCK in brain in the control of feeding behavior.